The mechanism of prostacyclin mediated relaxation and an epoxymethano analog (of prostaglandin endoperoxides)-mediated contraction of pulmonary vascular smooth muscle will be evaluated utilizing measurement of divalent ion fluxes, the binding of radio-labeled prostacyclin and the endoperoxide analogue, and mechanical force and tension development. The effects of these compounds on magnesium transport will be evaluated in relation to their ability to alter magnesium channels in pulmonary vascular smooth muscle and the ability of magnesium to alter the affinity of these substances for their receptor sites. The role of endogenous prostacyclin, thromboxane and prostaglandin on pulmonary vascular smooth muscle tone and electrolyte movement will be evaluated with the selective inhibition, sequentially, of PGI, thromboxane and finally prostaglandin, and simultaneously measuring the movement of divalent and monovalent ions. Finally, the role of the pulmonary vascular endothelium on these processes will be evaluated with the technique of mechanical destruction of the pulmonary venous and arterial endothelium and subsequent evaluation of neurotransmision, ion transport and prostaglandin synthesis in endothelial rich and endothelial deficient pulmonary vascular smooth muscle. These studies should provide a clear insight into the factors regulating pulmonary vascular smooth muscle tone and electrolyte transport.